Sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter, single-arm, phase 2 study.

Abstract

Systemic treatments are listed as first-line therapies for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), resulting in modest efficacy. We aimed to evaluate the efficacy and safety of sintilimab plus bevacizumab combined with radiotherapy (Sin-Bev-RT) in HCC with PVTT and to identify prognostic biomarkers. This open-label, multicenter, single-arm, phase 2 clinical trial was conducted at three tertiary hospitals in China. A total of 46 HCC patients with PVTT were enrolled. All the patients received the first cycle of intravenous sintilimab (200mg, day 1) plus bevacizumab (15mg/kg, day 1) within 3 days after enrollment. Radiotherapy (30-50Gy/10 fractions) was administered after 2 cycles of Sin-Bev. Sin-Bev was disrupted during radiotherapy and resumed 2 weeks after radiotherapy and continued every 3 weeks thereafter until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR). Patients obtained an ORR of 58.7% and a disease control rate of 100%. After a median follow-up time of 26.0 months (95% CI: 24.0-26.0), the median overall survival (OS) was 24.0 months (95% confidence interval [CI]: 19.0-not applicable) and the median progression-free survival (PFS) was 13.8 months (95% CI: 12.0-21.0), respectively. No unexpected adverse events or treatment-related deaths occurred. Mutations of PCTMD1 were predictive of shorter OS and PFS. Sintilimab plus bevacizumab combined with radiotherapy provides favorable treatment response and survival outcomes along with an acceptable safety profile in the first-line setting for HCC patients with PVTT. (ClinicalTrials.gov Identifier: NCT05010434).